Impurity Exclusion and Retention during Crystallisation and Recrystallisation — The Phenacetin by Ethylation of Paracetamol Process

Horgan, Danielle E.; Crowley, Lorraine M.; Stokes, Stephen; Lawrence, Simon E.; Moynihan, Humphrey A.

doi:10.5772/59715

Cited by 8 publications

(10 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 6 , 33 The even distribution of the impurity paracetamol in phenacetin crystals was shown by stepwise dissolution of large single crystals, which is hypothesized to be due to formation of a solid solution. 33 Ineffective purification of phenanthrene in the presence of impurity 9,10-dihydroanthracene by crystallization due to partial solid-solution formation between the components was demonstrated by analysis of the binary phase diagrams. 34 Partial miscibility between a pair of α- and β-epimers (2.6% for α in β and 4.4% for the reverse) was revealed by construction of binary phase diagrams and subsequent Tammann triangle plots.…”

Section: Impurities In Crystallizationmentioning

confidence: 99%

“…Such solid-state miscibility, whereby the impurity is thermodynamically substituted irregularly into the crystal lattice due to structurally similarity, is characterized by a distribution of the impurity throughout bulk crystal material. , The even distribution of the impurity paracetamol in phenacetin crystals was shown by stepwise dissolution of large single crystals, which is hypothesized to be due to formation of a solid solution . Ineffective purification of phenanthrene in the presence of impurity 9,10-dihydroanthracene by crystallization due to partial solid-solution formation between the components was demonstrated by analysis of the binary phase diagrams .…”

Section: Impurities In Crystallizationmentioning

confidence: 99%

See 1 more Smart Citation

A Structured Approach To Cope with Impurities during Industrial Crystallization Development

Urwin

Levilain

Marziano

et al. 2020

Org. Process Res. Dev.

View full text Add to dashboard Cite

The perfect separation with optimal productivity, yield, and purity is very difficult to achieve. Despite its high selectivity, in crystallization unwanted impurities routinely contaminate a crystallization product. Awareness of the mechanism by which the impurity incorporates is key to understanding how to achieve crystals of higher purity. Here, we present a general workflow which can rapidly identify the mechanism of impurity incorporation responsible for poor impurity rejection during a crystallization. A series of four general experiments using standard laboratory instrumentation is required for successful discrimination between incorporation mechanisms. The workflow is demonstrated using four examples of active pharmaceutical ingredients contaminated with structurally related organic impurities. Application of this workflow allows a targeted problem-solving approach to the management of impurities during industrial crystallization development, while also decreasing resources expended on process development.

show abstract

Section: Impurities In Crystallizationmentioning

confidence: 99%

Section: Impurities In Crystallizationmentioning

confidence: 99%

A Structured Approach To Cope with Impurities during Industrial Crystallization Development

Urwin

Levilain

Marziano

et al. 2020

Org. Process Res. Dev.

View full text Add to dashboard Cite

show abstract

“…Often multistep successive crystallizations are needed to reach a desired purity, significantly lowering the product yield. Many reports in the literature describe the effect of structurally related impurities or additives (so-called tailor-made additives) on the shape and crystallization behavior of organic crystals. − They may influence nucleation and growth, , and thus crystal shape, size, , and polymorphic outcome ,, and become incorporated into the structure. ,, However, data on the influence of impurities and crystallization parameters on purification of crystalline products together with their influence on crystal size, shape, and structure are limited in the literature. − …”

Section: Introductionmentioning

confidence: 99%

Process Parameters in the Purification of Curcumin by Cooling Crystallization

Ukrainczyk

Hodnett

Rasmuson

2016

Org. Process Res. Dev.

View full text Add to dashboard Cite

Purification of crude curcumin by up to four successive cooling crystallizations has been investigated for a wide variety of process conditions. For each crystallization step the influence of various processing conditions on crystal purity, polymorphic outcome, and crystal size and shape is reported. By an extensive number of experiments according to a statistical experimental design, the influence on cooling rate, seeding, seed polymorph, and agitation conditions has been identified. Slow cooling and seeding, particularly with the metastable Form II seed, significantly improves the purification. A correlation between product crystal size and purity is found. By tuning the crystallization parameters the number of recrystallization steps required to reach a certain purity can be reduced, which significantly increased the overall curcumin yield from 28% to 50%.

show abstract

“…However, some solid solutions have been observed in systems with structurally similar impurities. 53,55–60…”

Section: Impurity Incorporation In Solution Crystallizationmentioning

confidence: 99%

Impurity incorporation in solution crystallization: diagnosis, prevention, and control

2022

View full text Add to dashboard Cite

show abstract

Impurity Exclusion and Retention during Crystallisation and Recrystallisation — The Phenacetin by Ethylation of Paracetamol Process

Cited by 8 publications

References 26 publications

A Structured Approach To Cope with Impurities during Industrial Crystallization Development

A Structured Approach To Cope with Impurities during Industrial Crystallization Development

Process Parameters in the Purification of Curcumin by Cooling Crystallization

Impurity incorporation in solution crystallization: diagnosis, prevention, and control

Contact Info

Product

Resources

About